Advancements in the oral delivery of Docetaxel: challenges, current state-of-the-art and future trends

Abstract

The oral delivery of cancer chemotherapeutic drugs is challenging due to low bioavailability, gastrointestinal side effects, first-pass metabolism and P-glycoprotein efflux pumps. Thus, chemotherapeutic drugs, including Docetaxel, are administered via an intravenous route, which poses many disadvantages of its own. Recent advances in pharmaceutical research have focused on designing new and efficient drug delivery systems for site-specific targeting, thus leading to improved bioavailability and pharmacokinetics. A decent number of studies have been reported for the safe and effective oral delivery of Docetaxel. These nanocarriers, including liposomes, polymeric nanoparticles, metallic nanoparticles, hybrid nanoparticles, dendrimers and so on, have shown promising results in research papers and clinical trials. The present article comprehensively reviews the research efforts made so far in designing various advancements in the oral delivery of Docetaxel. Different strategies to improve oral bioavailability, prevent first-pass metabolism and inhibition of efflux pumping leading to improved pharmacokinetics and anticancer activity are discussed. The final portion of this review article presents key issues such as safety of nanomaterials, regulatory approval and future trends in nanomedicine research.

Keywords: P-glycoproteins; anticancer; efflux pump; first-pass metabolism; permeability enhancement; solubility enhancement.

Figure 1

(A) Chemical structure of Docetaxel and (B) graphical representation of the mechanism of action of Docetaxel.

Figure 2

Nanotechnology based emerging trends reported for the oral delivery of anticancer agents. Abbreviation: SEDDS, self-emulsifying drug delivery systems.

Figure 3

Different cellular mechanisms involved in the cellular uptake and permeation of various nanoformulations across the enterocytes after oral administration.